TY - JOUR

T1 - Evolution of anti-parkinsonian activity of monoterpenoid (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol in various in vivo models

AU - Valdman, Elena

AU - Kapitsa, Inga

AU - Ivanova, Еlena

AU - Voronina, Tat`iana

AU - Ardashov, Oleg

AU - Volcho, Konstantin

AU - Khazanov, Veniamin

AU - Salakhutdinov, Nariman

N1 - Publisher Copyright: © 2017 Elsevier B.V.

PY - 2017/11/15

Y1 - 2017/11/15

N2 - It has been found recently that monoterpenoid (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol (Diol) demonstrates high antiparkinsonian activity in some animal models. We carried out an extended study of the antiparkinsonian activity of Diol in a set of relevant animal models. Diol (20 mg/kg) exhibited an anticataleptogenic effect in the haloperidol-induced catalepsy model and restored motor activity in animals in the reserpine-induced model of oligokinesia. The ability of Diol singly administered before MPTP injection to reduce rigidity comparable to that of activity of L-DOPA (100 mg/kg) was found using the model of Parkinsonian syndrome (PS) induced by single injection of MPTP (30 mg/kg) to C57BL/6 mice. In the model of PS induced by subchronic administration of MPTP (4 × 20 mg/kg), Diol at a dose of 20 mg/kg reduced rigidity with effectiveness comparable to that of L-DOPA, while being superior to L-DOPA in terms of its effect on motor activity. It was found using the model of PS induced by systemic administration of rotenone that subchronic daily oral administration of Diol prior to rotenone injection reduced severity of PS in rats. Assessment of the effects of chronic administration of Diol (20 mg/kg) and L-DOPA to animals with 6-OHDA-induced PS showed that administration of Diol alleviated the symptoms of sensorimotor deficit in right limbs in rats. Thus, the potent antiparkinsonian activity of Diol was demonstrated in all the used rodent models experiments. Diol (20 mg/kg) is as effective as the comparator agent L-DOPA administered at doses of 50–100 mg/kg.

AB - It has been found recently that monoterpenoid (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol (Diol) demonstrates high antiparkinsonian activity in some animal models. We carried out an extended study of the antiparkinsonian activity of Diol in a set of relevant animal models. Diol (20 mg/kg) exhibited an anticataleptogenic effect in the haloperidol-induced catalepsy model and restored motor activity in animals in the reserpine-induced model of oligokinesia. The ability of Diol singly administered before MPTP injection to reduce rigidity comparable to that of activity of L-DOPA (100 mg/kg) was found using the model of Parkinsonian syndrome (PS) induced by single injection of MPTP (30 mg/kg) to C57BL/6 mice. In the model of PS induced by subchronic administration of MPTP (4 × 20 mg/kg), Diol at a dose of 20 mg/kg reduced rigidity with effectiveness comparable to that of L-DOPA, while being superior to L-DOPA in terms of its effect on motor activity. It was found using the model of PS induced by systemic administration of rotenone that subchronic daily oral administration of Diol prior to rotenone injection reduced severity of PS in rats. Assessment of the effects of chronic administration of Diol (20 mg/kg) and L-DOPA to animals with 6-OHDA-induced PS showed that administration of Diol alleviated the symptoms of sensorimotor deficit in right limbs in rats. Thus, the potent antiparkinsonian activity of Diol was demonstrated in all the used rodent models experiments. Diol (20 mg/kg) is as effective as the comparator agent L-DOPA administered at doses of 50–100 mg/kg.

KW - 6-OHDA

KW - Levodopa

KW - MPTP

KW - Parkinson disease

KW - Rotenone

KW - Terpene

KW - SERIES

KW - RATS

KW - MOUSE MODEL

KW - DISEASE

KW - ANIMAL-MODELS

KW - MICE

KW - BRAIN

KW - Antiparkinson Agents/pharmacology

KW - Oxotremorine/pharmacology

KW - Mice, Inbred C57BL

KW - Reserpine/pharmacology

KW - Parkinsonian Disorders/drug therapy

KW - Male

KW - Cyclohexanols/pharmacology

KW - Catalepsy/drug therapy

KW - Animals

KW - Mice

KW - Disease Models, Animal

UR - http://www.scopus.com/inward/record.url?scp=85030244099&partnerID=8YFLogxK

U2 - 10.1016/j.ejphar.2017.09.022

DO - 10.1016/j.ejphar.2017.09.022

M3 - Article

C2 - 28939292

AN - SCOPUS:85030244099

VL - 815

SP - 351

EP - 363

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

ER -